Bempedoic Acid (ETC-1002): an Investigational Inhibitor of ATP Citrate Lyase

Ozlem Bilen, Christie M Ballantyne, Ozlem Bilen, Christie M Ballantyne

Abstract

Bempedoic acid (ETC-1002), a novel therapeutic approach for low-density lipoprotein cholesterol (LDL-C) lowering, inhibits ATP citrate lyase (ACL), an enzyme involved in fatty acid and cholesterol synthesis. Although rodent studies suggested potential effects of ACL inhibition on both fatty acid and cholesterol synthesis, studies in humans show an effect only on cholesterol synthesis. In phase 2 studies, ETC-1002 reduced LDL-C as monotherapy, combined with ezetimibe, and added to statin therapy, with LDL-C lowering most pronounced when ETC-1002 was combined with ezetimibe in patients who cannot tolerate statins. Whether clinically relevant favorable effects on other cardiometabolic risk factors such as hyperglycemia and insulin resistance occur in humans is unknown and requires further investigation. Promising phase 2 results have led to the design of a large phase 3 program to gain more information on efficacy and safety of ETC-1002 in combination with statins and when added to ezetimibe in statin-intolerant patients.

Keywords: ETC-1002; Low-density lipoprotein cholesterol.

Conflict of interest statement

Ozlem Bilen declares no conflict of interest. Christie M. Ballantyne declares consultant fees, grants, and research support from Esperion, paid to her institution, during the conduct of the study; she also declares grants, research support, and/or consultant fees from Amarin, Amgen, Eli Lilly, Otsuka, Novartis, Pfizer, Regeneron, Sanofi-Synthelabo, Takeda, National Institutes of Health, American Heart Association, and American Diabetes Association; she also declares consultant fees from AstraZeneca, Ionis, Genzyme, Matinas BioPharma, and Merck. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.

Figures

Fig. 1
Fig. 1
Major metabolic pathways affected by bempedoic acid (ETC-1002) in humans as supported by clinical trial data. Animal data suggested additional effects on triglyceride metabolism via ACL inhibition and other cardiometabolic pathways via AMP-activated protein kinase (AMPK) activation. ACL ATP citrate lyase, Acetyl-CoA acetyl coenzyme A, HMG-S HMG-CoA synthase, HMG-R HMG-CoA reductase

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